Acute asthma exacerbation

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An asthma exacerbation is the acute worsening of asthma symptoms caused by reversible lower airway obstruction. The diagnosis is usually clinical and should involve early evaluation of the severity of asthma exacerbation. Complementary diagnostic studies include peak expiratory flow rates (PEFR), arterial blood gas, and, in some cases, chest x-ray. Immediate treatment is essential as asthma exacerbations can be life-threatening and may progress to respiratory arrest. The pillars of treatment are oxygen therapy, bronchodilators (short-acting β₂-agonists or SABA; short-acting muscarinic antagonists or SAMA), and corticosteroids, which are administered based on the severity of the exacerbation. After the acute exacerbation is under control, close follow-up and long-term treatment should be continued to reduce the risk of recurrence (see “Asthma” for details regarding long-term management).

The information in this article applies to patients older than 5 years of age.

The definitions listed here are for patients older than 5 years of age.

• Asthma exacerbation: a typically reversible episode of lower airway obstruction (bronchospasm) characterized by a worsening of asthma symptoms within a short period of time (acute or subacute) and accompanied by a change in baseline lung function. ^[2]
• Bronchospasm: a constriction in the bronchial muscles that results in airway obstruction within seconds to minutes. It is the characteristic symptom of asthma exacerbations, but it may also be triggered by certain medications or mechanical ventilation.
• Status asthmaticus: : a term used to describe severe asthma exacerbations that progress rapidly and do not respond to standard acute asthma therapy ^[3]

Asthma exacerbations occur when a patient with underlying asthma is exposed to a trigger. See “Etiology” in “Asthma” for a detailed list of triggers.

Risk factors for fatal or nearly-fatal asthma exacerbations ^[4][5][6]

• Asthma history
  • History of previous near-fatal asthma episode (e.g., requiring intubation, respiratory acidosis, ICU admission)
  • Hospital admission for asthma exacerbation
  • Multiple visits to the emergency department for asthma exacerbations in the past year
  • Medication-related factors
    • Need for ≥ 3 medications for asthma control
    • Current use or recent discontinuation of oral corticosteroids
    • No current use of inhaled corticosteroids
    • Heavy reliance on or increased frequency of need for SABA
• Comorbidities
  • Cardiovascular or respiratory disease: e.g., pneumonia, cardiac arrhythmias
  • Psychiatric disease or psychosocial factors
  • Other: obesity, diabetes mellitus, food allergies
• Behavioral or psychosocial features
  • Nonadherence to treatment, monitoring, and follow-up appointments
  • Social risk (e.g., isolation, precarious employment)
  • Alcohol or substance use disorder

Signs and symptoms vary depending on the severity of asthma exacerbation. For some patients, an acute exacerbation may be the first manifestation of asthma. ^[2][3]

• Common symptoms
  • Dyspnea
  • Increased coughing
• Vital signs and general appearance
  • Tachypnea
  • Tachycardia
  • Pulsus paradoxus
  • Hypoxemia; (low SpO₂, possible cyanosis)
  • Altered mental status
• Signs of bronchoconstriction
  • Prolonged expiratory phase
  • Expiratory wheezing
  • Silent chest
  • Hyperresonance on percussion
  • Inferior displacement and poor movement of the diaphragm
• Signs of increased work of breathing (WOB): e.g., use of accessory muscles

Features characteristic of imminent respiratory arrest include silent chest, altered mental status, bradycardia, paradoxical breathing, respiratory muscle exhaustion, and signs of respiratory failure on ABG (e.g., normalization of pH and P_aCO₂ in a fatiguing patient). ^[2]

Crackles on auscultation are rare in asthma exacerbations and may indicate a viral or bacterial trigger (e.g., pneumonia). ^[2]

The diagnosis of an acute asthma exacerbation is mainly clinical. Diagnostic studies are required to assess the severity of asthma exacerbation as well as to evaluate for potential underlying causes and/or differential diagnoses of dyspnea.

Pulmonary function tests ^[2]

• Indication: before initiating treatment for acute asthma exacerbation (only if rapidly available and tolerated by the patient)
• Objective
  • To assess severity at presentation
  • To monitor response to initial treatment
• Modalities
  • Spirometry: more reliable measurement, but may not be feasible during exacerbations
  • Peak flow meter; : easier to obtain in emergency situations; only measures PEFR
• Supportive findings
  • PEFR lower than baseline (see “Severity assessment in asthma exacerbation” for detailed interpretation)
  • Decreased FEV₁
• Special consideration: may not be feasible in life-threatening asthma and in young children

Do not delay treatment to complete assessment of lung function.

Arterial blood gas ^[2]

• Indications
  • PEFR or FEV₁< 50% predicted
  • Poor response to acute asthma therapy
  • Clinical worsening
• Initial findings
  • Respiratory alkalosis
  • Hypoxemia may be present.
• Late findings (indicative of a severe exacerbation)
  • Respiratory acidosis
  • Severe hypoxemia (P_aO₂ < 60 mm Hg)
  • Hypercapnia (P_aCO₂ > 40–45 mm Hg)

Patients with acute asthma exacerbations initially have hypocapnia (↓ P_aCO₂) and respiratory alkalosis (↑ pH) due to tachypnea. Rising PaCO₂ and normalizing pH in a patient with respiratory muscle fatigue are signs of impending respiratory failure!

Chest x-ray ^[2]

Not routinely required

• Indications
  • Suspicion of comorbid illness (e.g., pneumonia, pneumothorax)
  • Evaluation of differential diagnoses (e.g., ARDS, CHF, foreign body aspiration)
• Supportive findings
  • Signs of pulmonary hyperinflation
    • Horizontal appearance of ribs
    • Increased number of ribs above diaphragm level
    • Flat diaphragm
  • Bronchial thickening
  • Signs of other concomitant illnesses, if present

Additional diagnostic studies ^[6]

• Laboratory studies
  • CBC: Consider if there is suspicion of concomitant pneumonia.
  • BMP: Consider for patients already being treated with SABAs and/or corticosteroids.
• ECG (baseline)
  • Patients > 50 years old
  • Patients with COPD or cardiovascular comorbidities (e.g., coronary artery disease)

In patients with acute asthma, consider the possibility of complicating concomitant factors such as pneumonia, atelectasis, or pneumothorax.

The following conditions manifest as sudden dyspnea with/without altered breath sounds. ^[7]

• Anaphylaxis
• Acute bronchitis
• Foreign body aspiration
• Pulmonary embolism
• Pneumothorax
• Pneumonia
• Acute heart failure
• Sudden tracheal or bronchial compression
• Allergic bronchopulmonary aspergillosis
• Vocal cord dysfunction
• Dysfunctional breathing disorder (e.g., hyperventilation, thoracic dominant breathing) ^[8]
• Specific to infants or young children
  • Bronchiolitis (children < 2 years old; caused by RSV)
  • Laryngotracheomalacia (infants; causes inspiratory stridor)
  • Bronchopulmonary dysplasia (in premature infants)
  • See also “Wheezing in children”.
  • Croup
• See also “Differential diagnosis of dyspnea”.

The differential diagnoses listed here are not exhaustive.

Approach ^[2][4][6]

Use appropriate PPE as viral infections are a common trigger for asthma exacerbations.

• ABCDE approach
• Signs of life-threatening asthma exacerbation
  • Consider early intubation.
  • Administer SABA + SAMA + IV corticosteroids; consider IV magnesium
  • See “Imminent respiratory arrest in asthma” for details.
• No signs of life-threatening asthma at presentation
  • Rapidly obtain a focussed history, examination, PEFR, and pulse oximetry reading to assess severity.
  • Stratify the severity of asthma exacerbation.
• Administer initial medical therapy according to severity (see relevant sections below for details).
  • Severe asthma exacerbation: Supplemental O₂ + SABA + SAMA + oral/IV corticosteroids; consider IV magnesium
  • Moderate asthma exacerbation: Supplemental O₂ + SABA; consider oral corticosteroids
  • Mild asthma exacerbation: SABA; consider oral corticosteroids
• Monitor closely and escalate treatment accordingly.
• Consider fluid repletion (preferably oral) in infants and young children
• Order diagnostic tests as needed once stabilized.

Oxygen therapy, bronchodilators, and if needed, corticosteroids form the basis of initial therapy of an acute asthma exacerbation

Intubation in acute severe asthma is risky and challenging. It should be performed by an experienced practitioner whenever possible.

Severe asthma exacerbations can be life-threatening! Do not delay immediate treatment measures for diagnostic testing.

COVID-19 considerations ^[2]

• Avoid withdrawing inhaled corticosteroids in patients who regularly take them. ^[9]
• Minimize viral transmission.
  • MDI with spacers are preferred; avoid nebulizers, if feasible, in patients with suspected/confirmed COVID-19. ^[2]
  • If NIPPV is attempted, a helmet interface should be used whenever possible.
• See “COVID-19” for further information.

Monitoring ^[4][6]

• Assess response to initial treatment
  • Perform serial examinations to assess symptom severity and physical examination findings.
  • Measure pulmonary function after 1 hour of initial treatment.
  • Frequently monitor vitals, O₂ saturation, and PCO₂ levels.
  • Consider continuous cardiac and pulse oximetry monitoring in patients with risk factors for fatal or nearly fatal asthma exacerbations.
• Stratify response to therapy: Evaluate post-treatment parameters to guide decisions on further treatment and disposition.

Disposition ^[2][4][6]

Disposition is determined by the severity of asthma exacerbation at presentation as well as response to initial therapy.

• ICU admission
  • Life-threatening asthma at presentation
  • Any severity with poor response to acute asthma therapy
• Ward admission: mild, moderate, or severe asthma exacerbation at presentation with either of the following
  • Risk factors for fatal or nearly fatal asthma
  • Incomplete response to acute asthma therapy
• Discharge
  • Consider if all of the following parameters are met:
    • Mild or moderate asthma exacerbation at presentation
    • Good response to acute asthma therapy sustained for ≥ 60 minutes
    • Ability to complete treatment at home
  • Advice at discharge (medications, patient education): See “Reduction of relapse risk” in “Treatment.”
  • Follow-up: recommended within 2–7 days; earlier if symptoms recur

• There are several severity assessment scores for acute exacerbation of asthma that can be used to guide treatment decisions and disposition.
• The following severity assessment is based on the 2007 National Asthma Education and Prevention Program (NAEPP) guidelines.

Early recognition of hypercapnic respiratory failure and/or hypoxemic respiratory failure is vital.

Approach ^[2][6]

Urgently consult critical care team and respiratory therapist.

Apneic or comatose patients

• Administer intubation induction agent (preferably ketamine ). ^[10]
• Intubate; experienced practitioner preferred (see “Intubation and mechanical ventilation in asthma” for details).
• Start mechanical ventilation with 100% oxygen using a ventilation strategy for obstructive lung disease.
• Administer bronchodilators via ventilator tubing and IV corticosteroids (see “Initial medical therapy for life-threatening asthma”).

All other patients ^[4][6]

• Prepare for intubation early (i.e., have equipment and induction agents ready).
• Maximize oxygen delivery (100% oxygen) via NRB.
• Initial medical therapy for life-threatening asthma
  • Nebulized SABA (albuterol; intermittent nebulizer OR continuous nebulized albuterol )
  • Plus nebulized SAMA (ipratropium bromide nebulizer )
  • Plus IV corticosteroids (prednisolone or methylprednisolone ) ^[6]
• Consider a single dose of IV magnesium sulfate in the following situations: ^[4]
  • Persistent hypoxemia after initial therapy
  • Adults with FEV < 25–30% at presentation
  • Children with FEV < 60% after 1 hour of treatment
• Other options for refractory asthma include heliox and advanced adjunctive therapies (in consultation with a specialist). ^[6]
• No improvement or signs of respiratory failure : Intubate; see “Intubation and mechanical ventilation in asthma” for details.
• Admit to critical care unit for monitoring and further management.

Although efforts should be maximized to prevent the need for mechanical ventilation, intubation should not be delayed once an indication to intubate in asthma is identified. Anticipate and plan for intubation prior to the onset of complete respiratory failure, due to the risks and difficulties of the procedure. ^[6]

Intubation and mechanical ventilation in asthma

NIPPV can be used as a bridge to intubation, as it may be more effective for preoxygenation than NRB. More research is required before NIPPV can be recommended as a method of preventing intubation. Consult a critical care specialist if considering NIPPV.

Intubation ^[5][6]

• Indications for intubation in asthma include: ^[5]
  • Cardiac/respiratory arrest
  • Life-threatening asthma exacerbation not responding to initial medical therapy
  • Imminent respiratory arrest despite maximal treatment, as evidenced by:
    • Persistent or worsening hypoxia
    • Persistent or worsening hypercapnia
    • Respiratory acidosis
    • Worsening of mental status
  • Experienced clinician judgment: based on a multifactorial estimate of the likelihood of progression to respiratory failure
• Associated risks
  • Worsening of bronchospasm
  • Increased periintubation mortality
    • Hypoxic brain injury
    • Cardiac arrest
    • Circulatory collapse
• Recommendations
  • Ketamine is the preferred induction agent in asthma exacerbations (see “Intubation medications” for more details).
  • Intubation by an experienced practitioner is recommended.
  • See “High-risk indications for mechanical ventilation” for periintubation risk reduction.

Invasive mechanical ventilation

• Associated with a high rate of complications
• See “Ventilation strategies for obstructive lung disease” for information on preferred ventilation settings for adults.
• Permissive hypercapnia is typically applied to prevent barotrauma and other ventilator-induced lung injury.
• See “Troubleshooting of mechanical ventilation” for strategies to optimize gas exchange and management of complications (e.g., hemodynamic impairment, dynamic hyperinflation).

Continue bronchodilator therapy even when patients are mechanically ventilated.

Initial treatment ^[2][4][6]

• Supplemental O₂
  • Start with 100% O₂ via NRB.
  • Titrate down as needed to attain target SpO₂ ^[2]
    • Children: 94–98%
    • Adults: 93–95%
• Plus bronchodilators
  • High-dose inhaled SABA: albuterol MDI with spacer , OR intermittent nebulizer , OR continuous nebulized albuterol ^[6]
  • Plus high-dose inhaled SAMA; : Ipratropium bromide MDI with spacer , OR ipratropium bromide nebulizer
• Plus corticosteroids ^[6]
  • Oral corticosteroids (prednisone ) are preferable.
  • IV corticosteroids (prednisolone or methylprednisolone ) are suitable in patients unable to swallow or with impaired gastrointestinal absorption and/or transit time.
• No improvement within 1 hour of initial medical therapy: Consider IV magnesium sulfate and/or heliox. ^[4][6]

Higher doses of corticosteroids do not relate to better outcomes in severe exacerbations. ^[6]

Treatment escalation ^[2][4][6]

• Indications
  • Poor response to acute asthma therapy
  • Drowsiness/confusion
  • Pronounced signs of increased WOB
• Measures
  • Consult ICU.
  • Consider advanced adjunct therapies in consultation with a respiratory specialist.
  • Signs of life-threatening asthma: Consider mechanical ventilation; see “Imminent respiratory arrest in asthma.”

Initial treatment ^[2][4][6]

• Supplemental O₂
  • Start with a nasal cannula or simple face mask oxygen.
  • Titrate up as needed to attain target SpO₂ ^[2]
    • Children: 94–98%
    • Adults: 93–95%
• High-dose inhaled SABA: albuterol MDI with spacer , OR albuterol nebulizer ^[6]
• Oral corticosteroids (indicated in most patients): e.g., prednisone ). ^[6]

Treatment escalation ^[2][4][6]

• Poor response to acute asthma therapy: Manage as severe exacerbation.

Initial treatment ^[2][4][6]

• Supplemental O₂if SpO₂ at presentation is < 94% in children or < 93% in adults
• Inhaled SABA: albuterol nebulizer or albuterol MDI with spacer ^[6]
• No immediate response to SABA; ; recent use of oral steroids: Consider oral corticosteroids (prednisone). ^[6]

Treatment escalation ^[2][4][6]

• Incomplete response to acute asthma therapy: Manage as a moderate exacerbation.
• Poor response to acute asthma therapy: Manage as a severe exacerbation.

Treatment goals

• Correction of hypoxemia (see “Short-term oxygen therapy” and “Basic oxygen delivery systems”)
• Reversal of lower airway obstruction with bronchodilators
• Reduction of relapse risk

Overview of initial treatment of acute asthma

Follow a stepwise approach to initial pharmacotherapy and adjust treatment according to clinical response with serial evaluations and monitoring. See relevant sections above for details on drugs and dosages. ^[2][6]

Short-acting beta-2 agonist (SABA) ^[2][6]

• Indication: recommended for all patients with asthma exacerbations
• Administration
  • Nebulizer
    • Preferred in severe crisis and in patients who are unable or refuse to use an inhaler ^[6]
    • There is no evidence to favor continuous over intermittent nebulization. ^[2]
  • Pressurized metered-dose inhaler plus spacer (valved holding chamber)
    • Preferred in mild/moderate crisis
    • No aerosol dissemination ^[2]
    • Effective delivery system (reaches doses equivalent to nebulizer) ^[6]
• Agents: Selective SABAs are preferred, e.g., albuterol. ^[2][6]
• Response
  • Onset of action: < 5 minutes
  • Significant clinical improvement: typically expected after 3 initial doses (i.e., in 1 hour).
  • No improvement : Escalate treatment.

Frequent administration of an inhaled SABA is the treatment of choice to reverse airway obstruction caused by bronchospasm.

Systemic corticosteroids ^[2][6]

• Indication ^[2]
  • All asthma exacerbations in patients > 6 years of age (with the possible exception of very mild episodes).
  • Recommended within the first hour of presentation
• Agents and administration
  • Oral therapy (e.g., prednisone): rapid administration; good bioavailability ^[2]
  • Parenteral therapy (e.g., prednisolone, methylprednisolone): Consider in patients who cannot swallow. ^[2]
  • See “Relative potency of corticosteroids” for equivalents.
• Response: effects expected in ∼ 4 hours

Short-acting muscarinic antagonists (SAMA) ^[6]

• Indications
  • Emergency management of severe exacerbations
  • Consider for emergency management in moderate exacerbations.
• Administration
  • Use in combination with SABA.
  • Can be given via MDI or nebulizer
• Agent: Ipratropium bromide

IV magnesium sulfate ^[2]

• Indication: life-threatening asthma or severe asthma exacerbation
• Cautions: Monitor for signs of hypermagnesemia.

ASTHMA: Albuterol, STeroids, Humidified O₂, Magnesium (severe exacerbations), and Anticholinergics (ipratropium bromide) are the meds for asthma exacerbations.

Additional pharmacotherapy ^[2][6]

• Refractory severe exacerbations/imminent respiratory arrest: Consider the following under specialist guidance.
  • Continuous SABA nebulizer ^[2]
  • Helium oxygen therapy (heliox) ^[2][5]
  • IV β₂-agonists
  • IV leukotriene-receptor antagonists
• Associated anaphylaxis: Combine treatment with epinephrine; see “Management of anaphylaxis” for details. ^[2]
• Evidence of concomitant pneumonia : antibiotic therapy; see “Treatment of pneumonia” for details

The following therapies should be avoided, as their benefits are limited and outweighed by risks and side effects: theophylline, aminophylline, mucolytics, anxiolytics, and chest physiotherapy. ^[6]

Reduction of relapse risk ^[2][4]

• Inhalers
  • Continue SABA for symptom control. ^[6]
  • Consider initiating medium-dose inhaled corticosteroids (ICS) in select patients (see “Asthma treatment” for doses). ^[2][6]
• Systemic corticosteroids
  • Indicated if systemic corticosteroids were administered for acute management
  • Continue regimen initiated in the emergency room.
  • Recommended duration ^[4][6]
    • Adults: usually 5–7 days
    • Children: usually 3–5 days
• Patient education
  • Review and/or teach inhaler technique; emphasize the importance of spacers with MDIs.
  • Identify and avoid asthma triggers, if possible.
  • Review symptom recognition and reasons to seek care (e.g., increased need for rescue therapy).
  • Teach the use of a peak flow meter and the recording and interpretation of PEFRs.
  • Provide an individualized written action plan for patients and/or caregivers.

• Follow ABCDE approach.
• Rapidly screen for signs of life-threatening asthma (imminent respiratory arrest); if present:
  • Consult critical care.
  • Administer inhaled SABA + inhaled SAMA + IV corticosteroids.
  • Consider adjunctive therapies to prevent intubation (e.g., magnesium sulfate, heliox).
  • Administer induction agent (ketamine) and intubate early if indications for intubation in asthma are identified.
  • Use ventilation strategy for obstructive lung disease.
  • Continue treatment (e.g., administer bronchodilators via ventilator tubing).
• Assess severity of asthma exacerbation (clinical evaluation, PEFR, and ABG as needed).
• Provide supplemental O₂ to achieve/maintain target SpO₂ (i.e., 93–95% in adults; 94–98% in children).
• Administer acute asthma therapy according to severity (i.e., inhaled SABA ± oral/IV corticosteroids ± inhaled SAMA ± IV magnesium sulfate)
• Reassess severity frequently and escalate treatment as needed.
• Order diagnostic tests as needed once stabilized.
• Determine disposition (moderate/severe exacerbations: hospital/ICU admission; mild/moderate exacerbation: evaluate for discharge eligibility).
• Provide discharge medications and instructions.